Byssinosis is an occupational lung disease associated with the inhalation of cotton and other textile dusts. Whlile the acute phase of the disease has been characrized by reversible, across-shift changes in lung function and the chronic phase the presence of chronic bronchitis and/or abnormal lung function, the transition between the two stages of the disease remains poorly understood. The inflammatory potential of cotton bract on airways is now well established. Since increasing evidence suggests that airway inflammmtion is involved in the developmnt of air-way responsiveness, and that hyperresponsiveness may predispose to chronic airway disease, the broad objective of this investigation is to examine the effects of inhaled cotton bract extract (CBE) on non-specific airway hyperresponsiveness to methacholine. The specific aims which will be addressed include: 1) Characterize the development of airway hyperresponsiveness from CBE in smokers. This part of the study will involve healthy non-atopic nonsmokers, sex- and age-mtched to healthy non-atopic smokers. Smokers will be divided and matched into 2 paired groups whose members will average less than a 10 pack-year history or greater than 10 pack-year history. Methachoine tests will be performed 2 hours after exposures; 2) Examine the eftect ot repeated CBE exposures on the developrent of airway hyperresponsiveness; methacholine tests will performed following the first and fifth day of consecutive exposure days with CBE and again following a CBE exposure after a 2 day (e.g. weekend) absence ot provocation with CBE. CBE and methacholine provocations will be assessed by partial and maximal expiratory flow-volume (PEFV and MEFV) curves. The primary response parameter from methacholine challenge wiil be the concentration of drug that induces a 25% fall in flow rates at 40% of the vital capacity below total lung capacity on the PEFV curves PC25MEF40% [P] ). 'Ihese relationships may be important in understanding the natural history of byssinosis since airway hyperresponsiveness appears to play an important in the accelerated loss of lung function in patients with chronic airflow obstruction.